Processing of social information, such as socially rewarding (e.g., positive emotional expressions) and socially threatening (e.g., angry or fearful expressions) stimuli, is altered in a range of primary psychiatric disorders. Such alterations are increasingly recognized as important functional components of psychopathology. However, despite the fact that motivations to use drugs are closely linked with social context, little is known about whether drugs of abuse affect social processing, either acutely or longer-term. Anecdotally, many users report that drugs enhance social experiences, making interactions easier or more pleasurable;these purported effects appear to motivate some drug use. Acute alterations to social processing may, therefore, constitute an aspect of the reinforcing effects of certain, if not all, abused drugs. If this is true, this novel mechanism likely contributes to the initiation and/or maintenance of drug use and to individuals'preferences for certain drugs. Little controlled research has investigated the effects of drugs on social processing in humans. It thus remains largely unclear whether drug users'beliefs about socially enhancing drug effects are based in misperception or fact. This pilot study employs a powerful combination of functional imaging, acute drug administration and social neuroscience tasks to collect preliminary data characterizing the effects of two abused drugs, 13,4-methylenedioxymethamphetamine (MDMA;'ecstasy') and D9tetrahydrocannabinol (THC, the primary psychoactive component of marijuana), on social reward and social threat processing in humans. Healthy male and female volunteers (N=16), with recreational ecstasy and marijuana exposure, will undergo 3 sessions in which they will be administered oral MDMA (1.5 mg/kg), THC (10 mg), or placebo, before completing laboratory-based social processing measures. Measures will include standardized probes of social reward and social threat in a pharmacological functional Magnetic Resonance Imaging (phMRI) protocol, to assess drug effects on neural and behavioral processing of socially appetitive and aversive material. We will also measure subjective drug effects, focusing on sociability and social discomfort. We hypothesize that MDMA will 1) increase social reward responses and subjective sociability;and 2) reduce social threat responses and social discomfort. We hypothesize that THC will 1) reduce social threat responses and social discomfort;but will 2) have no effect on response to positive social material. Pilot data obtained will, in keeping with I/START aims, be employed to initiate a larger (R01) imaging investigation of the effects of a range of drugs, and doses, on social processing. Project results will contribute to scientific understandings of an under-researched acute drug effect that may affect: 1) interpersonal behavior, including risky behavior, while under the influence of drugs;2) individuals'preferences for certain drugs;and 3) initiation and/or maintenance of drug use. Thus, this project, which will initiate a comprehensive assessment of acute drug effects on social processing, has the potential for substantial impact. PUBLIC HEALTH RELEVANCE: Although some drug users report that they use drugs to make social interactions easier and more pleasurable, little is understood about the effects of drugs on social experiences. This pilot project uses a novel, multidimensional, imaging-based approach to study the effects of two drugs commonly used in social settings, MDMA ('ecstasy') and THC (found in marijuana), on social information processing in humans. We anticipate that results will improve scientific knowledge about social motivations to use drugs, ultimately contributing to better prevention and treatment for drug use.